Direct enhancement of gonadotropin-stimulated ovarian estrogen biosynthesis by estrogen and clomiphene citrate.
The biosynthesis of ovarian aromatases and hence estrogen production are under the control of the gonadotropins, FSH and LH. Using a primary culture of rat granulosa cells, we now report that estrogens (diethylstilbestrol and 17 beta-estradiol) augment the stimulation of aromatase activity by FSH and LH. Moreover, clomiphene citrate, a drug widely used to induce ovulation in anovulatory women, also enhances gonadotropin-stimulated aromatase activity. These in vitro findings suggest that estrogens within the microenvironment of the ovarian follicles may exert a local autoregulatory effect on their own production via an ultra-short loop, positive feedback mechanism. In addition, the clinical efficacy of clomiphene citrate may derive partially from its direct augmentation of the gonadotropin-stimulated estrogen production at the ovarian level.
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002996:Clomiphene / Q000031:analogs & derivatives* / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D045166:Estradiol Congeners / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D045166:Estradiol Congeners; D004967:Estrogens; D002996:Clomiphene; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D001141:Aromatase